A number of years ago it was commonly believed that rheumatoid arthritis had an infectious etiology. This view is not popular today, although the inflammatory features and constitutional manifestations of rheumatoid arthritis--the synovitis and granulomatous lesions, the fever, tachycardia, leukocytosis, lymphadenopathy and occasional spelnomegaly, the accelerated erythrocyte sedimentation rate and other changes in "acute phases reactants"--are all compatible with an infectious process. Competent and repeated bacteriologic studies have failed to recover consistently a single infectious agent from the blood, synovial fluid, synovial tissues or subcutaneous nodules. Attempts to transmit the disease by injecting joint fluid from patients with rheumatoid arthritis into the joints of other human subjects have been unsuccessful. Subcutaneous nodules have failed to survive following homologous transplantation (Bauer, et al, 1951) the Practitioner 166:5.
An infectious process may appear to precipitate the onset of rheumatoid arthritis in a significant number of patients, and may exert a deleterious influence on the course of the disease when it has already been established. There is statistical evidence to support this clinical impression (Lewis-Faning, 1950) Ann Rheum. Dis., Suppl. 9.
Many attempts have been made to produce a disease in animals similar to rheumatoid arthritis. While a variety of bacteria can produce arthritis in animals, they fail to reproduce the clinical and pathologic features of rheumatoid arthritis, particularly the self-perpetuating characters of the proliferative arthritis. Arthritis bearing some semblance to the human disease has been produced in mice by pleuro-pneumonia-like organisms (Sabin, 1939) Science 89:228, and in swine by Erysipelothrix rhusiopathiae (Sikes, et al, 1955). The concept that these organisms may initiate a hypersensitivity mechanism has been postulated (Sikes, et al, 1955).
Students of rheumatoid arthritis nevertheless continue to be intrigued by certain recurring themes that suggest relationships between infections and joint disease. Gonorrhea, for instance, is capable not only of producing typical gonorrheal arthritis but also of occasionally introducing chronic arthritis which evolved into typical rheumatoid arthritis. No statistics are available on the incidence with which this occurs, so one cannot know how much to stress the relationship. Tonsillitis or pharyngitis may also be followed by a polyarthritis, which at first appears to be rheumatic fever but which evolves into rheumatoid arthritis. Acute viral infections, especially rubella in young women, may be followed by persistent polyarthritides involving small joints as well as large; these arthritides generally run a several-month course of persisting joint disease resembling rheumatoid arthritis before gradually subsiding.
While chronic infection by an unknown agent remains a popular assumption for the etiology of rheumatoid arthritis, no published data exist to support the presumption. Some students of the disease suspect that if infection is a factor it may not be infection by any specific type of microorganism with an altered host response generated by the infections responsible for the disease. The present invention is based on this theory for the origin of rheumatoid arthritis.
Although an infectious etiology has never been established, several recent developments appear relevant in support of this theory.
Some of these are as follows:
1. Patients with rheumatoid arthritis have lower than normal levels of IgA, the class of immunoglobulin found in secretions of the gastrointestinal tract.
2. Immunoglobulin A produced in response to immunization via the salivary glands is found in serum colostrum and milk as well as in the saliva. It is suggested that the IgA is transported to these various fluids via the gastrointestinal tract and the lymphatic system (Michelok, et al, 1975) Proc. Soc. Exptl. Biol. Med. 148:1114.
3. Following an intestinal bypass operation for morbid obesity, certain patients develop symptoms that are virtually identical with rheumatoid arthritis. The onset of arthritis is accompanied by the appearance in blood serum of circulating cryoproteins composed of IgG, IgM, IgA, complement components C.sub.3, C.sub.4, C.sub.5, and IgG antibody against E. coli and B. fragilis. Removal of the intestinal bypass results in complete remission of the symptoms (Woods, et al, 1976) New Engl. J. Med. 294:121.
4. A type of Diplostreptococcus agalactiae belonging to the streptococci group B has been implicated as an etiologic agent in rheumatoid arthritis (Svartz, 1972) Acta. Med. Scand. 192:231. This streptococcus is present in most commercially available pasteurized milk but not in immune milk.
5. A predisposition to rheumatic disease appears to be inherited via the histocompatibility antigens (HL-A). These antigens probably determine host response to infective agents.
On the basis of this evidence, it is concluded that rheumatoid arthritis has an infectious origin; the site of infection occurs in the gut; a number of different bacterial strains are involved in the infection; the infection probably results because of a failure in the host's immune defense mechanism; and the most effective way to treat the disease is to re-establish the immune protection against the infectious agent in the gut.